We previously demonstrated limitation in great cardiac vein flow response to rapid atrial pacing following ergonovine administration in the absence of epicardial coronary artery disease or spasm, a syndrome we now call microvascular angina. To further study the effect of ergonovine on coronary flow reserve, we measured peak to basal flow velocity with papaverine 15 mg intracoronary, using a steerable Doppler catheter in the proximal left anterior descending artery in 5 patients with angina and angiographically normal coronary arteries. Although the initial peak to basal flow velocity response to papaverine 15 mg was normal (4.1 plus or minus 1.9, mean plus or minus 1 S.D.), after ergonovine .15 mg intravenously there was a significant fall in the peak to basal flow velocity response to the same dose of papaverine (4.1 plus or minus 1.9 to 3.4 plus or minus 1.6, p less than .05) and a significant increase in the coronary resistance index (30.5 plus or minus 13.9 to 37.6 plus or minus 15.2, p less than .05). Proximal left anterior descending artery dimensions after ergonovine did not change compared to after papaverine. Further, the 4 patients who had a decrease in peak to basal flow velocity after ergonovine were the same 4 who had chest pain and decreased great cardiac vein flow during pacing after ergonovine, compared to pacing alone, major criteria for microvascular angina. Thus, ergonovine decreases peak pharmacologic flow reserve in patients with microvascular angina, indicating vasoconstriction of the coronary microcirculation.